Mapa mental

Liver

Bertrand Ng VET377 Pathology Inglês

Mind map: Liver

Conteúdo do mapa

Liver

Clinical Signs
- Specific
  - Hepatomegaly
  - Microhepatica
  - Icterus
  - Ascites
  - Hepatoencephalopathy
- Non-Specific
  - Depression
  - Weight Loss/Anorexia
  - Vomiting
  - Abdominal Pain
  - PU/PD
  - Serum Biochemistry Diagnostic
    - ID Liver Disease
      - Hepatocyte Injury/necrosis
      - Alternations in synthesis or excretory function
      - Altered portal circulation
    - Acute or Chronic
    - Systemic Disease
    - Primary or Secondary to Hepatic Involvement
    - What to measure
      - Liver Enzymes
        Hepatocellular Leakage Enzymes
        Soluble: High Activity Released with Damage to membranes ALT/AST increase indicate LIVER DAMAGE, more with Acute, mild with Chronic
        Alanine Aminotransferase (ALT)
        Cytoplasmic Enzyme Highest activity in Hepatocytes and Striated (skeletal + cardiac) muscle 1/2 life Dogs: 60 hours 1/2 life Cats: <24 hours 
        Specific for Hepatic Injury (K9/F9)
        High activity in liver (K9/F9)
        Largies/pigs/birds, LOW activity, NOT good indicator
        Aspartate Aminotransferase (AST)
        Cytosolic and Mitochondrial High in Skeletal muscle/Kidney/Pancreas/RBCs High in both acute and chronic liver injury 1/2 life Dogs: 12 hours
        High activity in ALL species, in Acute AND Chronic liver injury
        High in SKELETAL MUSCLES, kidneys, RBCs
        Use CK to differentiate liver and muscle
        More severe cell injury/death
        Sorbitol Dehydrogenase (SDH)
        Liver of all domestic animals. LIVER SPECIFIC. Hepatocellular damage for largies 1/2 life <12 hours Activity declines rapidly after collection, so hurry the testing
        Liver Specific
        Good for Largies
        Glutamate Dehydrogenase (GLDH)
        Cytosolic enzyme Good for assessing liver damage: ruminants, or acute damage: horses
        With continued damage, GLDH eventually returns to normal
        Ornithine Carbamyltransferase (OCT)
        Liver specific in most domestic species Liver damage in cattle/Pigs Like ALT in dogs Uncommonly used (more pigs)
        Induced Enzymes
        Typically Membrane bound Not released into serum with increased membrane permeability Increased serum enzyme activity is the result of induction, because of cholestasis, drug or hormonal effects.
        Alkaline Phosphatase (ALP)
        Operate in alkaline environment Membrane bound enzymes, not released into circulation with increased permeability Useful prognostic indicator for canine osteosarcoma, and of toxic tubular injury in urine levels NO CORRELATION between severity and degree of increase Ruminants have wide reference ranges, so NOT USEFUL for biliary disease Cats: LOW activity and half life, so NOT USEFUL
        Isoenzymes
        Hepatic
        Higher activity in dogs than cats Cats ALP 1/2 life is 6 hours Dogs ALP 1/2 life is 72 hours Elevates in both acute/chronic disease Marked = CHOLESTASIS, w/ cholangitis/biliary cirrhosis/obstruction?
        Specific for Liver Disease
        Increases with intrahepatic/Extrahepatic Cholestasis
        Corticosteroid induced (DOGS ONLY)
        Screening test for hyperadrenocorticism in dogs
        Exogenous/Endogenous glucocorticoids cause increase
        Also drug induced/neoplasms or chronic metabolic disease induced
        Bone
        1/2 life is 72 hours
        Young/Rapid growers
        Animals with lytic/proliferative bone lesions
        Intestinal/Placental
        Half life <6 hours
        Not important in dogs/cats
        Important for colic horses
        Increases with late term pregnancy
        Not useful in Cats + Ruminants
        Gamma Glytamyl Transferase (GGT)
        Associated with microvilli of hepatocytes, biliary epithelial cells, renal tubular, mammary cells. Dogs 1/2 life = 3 days
        Caused by Cholestasis (esp. birds)
        Less sensitive, but MORE SPECIFIC than ALP (except in cats)
        Also corticosteroid induced in dogs
        High colostrum in dogs/ruminants > increased serum GGT
        Sample Collection/Handling
        Haemolysis causes mild ALT/AST increase
        Lipemia also causes increase in ALT
        Improper handling > Degradation > Decreased values
        Store <24h in fridge/rtp
        Don't freeze and thaw repeatedly
      - Total Bilirubin
      - Bile Acids
        Synthesised in hepatocytes from Cholesterol
        Conjugated, secreted in bile
        Emulsify fats
        Recycled via entero-hepatic circulation
        Can cause hepatocyte damage in cholestasis
        Testing
        Horses
        Single sample: NO gall bladder
        Ruminants
        Less sensitive, WIDE reference range
        Birds
        Like mammals, variable
        Test Liver Function
        Increased
        Portosystemic Shunts
        Liver Failure
        Cholestasis
        Inappropriate gall bladder contraction
        Small intestinal bacterial overgrowth
        Decreased
        Small Intestine malabsorption
        NOT Liver Failure. Does not decrease with liver failure
      - Albumin
        Made in Liver
        Long half life
        NOT affected by acute liver disease
        MAY occur with liver failure
        But HIGH functional mass loss before affected
        NOT a specific indicator of disease
        Hypoalbuminemia
        Malabsorption
        Whole Blood Loss
        Low albumin and globulins
        HYPERglobulinemia = chronic liver disease
        Protein losing enteropathy
        Inflammation/Starvation/Cachexia/Protein loss renal disease/burns/parasites/effusions
      - Glucose
        Affected by severe liver disease
        Liver = Gluconeogenesis + Glycogenolysis
        Loss (75%) = Hypoglycemia
      - Cholesterol
        Made and cleared in liver
        Cholestasis = Increased cholesterol
        End stage disease = decreased synthesis,
        LOW cholesterol
      - Urea
        Hepatic insufficiency = decreased urea output
        Reduced blood urea Nitrogen
      - Clotting Factors
        Vit. K Dependent
        II, VII, IX
        Decreased hepatic mass = decreased synthesis
        Short half life
        <30% = Long PT/APTT
        IMPORTANT TO CHECK BEFORE LIVER BIOPSY
Diagnostic Tests
- CBC
  - Mild, Poorly Regenerative Anemia
    - Microcytosis with PS shunts
    - Poikilocytosis
      - Schistocytes
      - Acanthocytes
      - Leptocytes
      - Target Cell (Fe deficiency)
  - Impaired platelet aggregation/function
- Liver Function Tests
- Urine Sample
- Liver Biopsy
- Abdominal Imaging
Jaundice/Hyperbilirubinemia
- Measure Bilirubin with other clinical data
- Causes
  - Pre-hepatic: haemolysis
    - Unconjugated (initially)
    - IMHA/infectious/Metabolic
  - Hepatic: Hepatic damage
    - Mixed (initially)
    - Usually severe, diffuse: cirrhosis, widespread degeneration
    - Any disease really: Hepatocyte injury (DAMNITV)
      - Numerous Causes
        Infection!
        Routes of Entry
        Hematogenous
        Biliary
        Direct Penetration
        Defence
        Kupffer cells/IgA
        Anatomical barriers: rib cage
      - Susceptible to hypoxia/metabolite disturbance
      - Releases:
        ALT
        AST
        SDH
        GLDH
        OCT
      - Patterns of Acute Degeneration
        Random Hepatocellular Degeneration
        single cell or multifocal
        INFECTIOUS AGENTS: B, V etc.
        e.g Salmonella
        "Paratyphoid nodules" random discrete necrotic foci with mØ
        e.g Tyzzer's Disease
        Clostridium piliforme
        Random, multifocal-coalescing necrosis
        bacilli and acute inflammation
        lab animals/foals/neonates/immunocompromised
        Zonal Hepatocellular Degeneration
        Regular/Diffuse pattern: defined regions
        Pale/friable/enlarged liver
        Enhanced lobular pattern
        Initial pallor (necrosis) of affected zone, becomes red (dilation/congestion of sinusoids)
        Types of Zonal Pattern
        Centrilobular degeneration
        Most common
        Periacinar
        Zone of hepatocytes around central vein
        Most susceptible to hypoxia
        Most drug metabolising ability
        Toxic or Hypoxic insult
        Paracentral degeneration
        Apex of acinus
        Direct-acting toxin or due to severe, acute anemia
        Midzonal degeneration
        Zone 2: MOST RARE
        Some toxins
        Periportal degeneration
        Periportal zone: Uncommon
        Direct acting toxins
        Toxins that don't require metabolism
        Bridging degeneration
        Variable across >2 zones
        Just confluence of necrotic areas
        Massive Necrosis (submassive)
        Often fatal
        Entire/contiguous lobules
        Severe toxic insult
        Amanita deathcap
        Vitamin E/Se deficiency
      - Acute Hepatitis
        Infectious/systemic infection
        Viruses: Herpes/FIP
        Bacteria: Salmonella/Tyzzer's
        Parasites: Toxoplasma
        Fungi: Zygomycetes
        Hepatocellular necrosis +/- apoptosis
        Examples
        Herpesvirus
        Abortigenic
        affects foetus livers
        random, small necrotic foci and multi organ inflamm.
        Canine Infectious Hepatitis
        Canine Adenovirus 1 (CAV-1)
        Acute, centrilobular necrosis and inflammation
        Widespread petechial/ecchymotic hemorrhage
        Campylobacteriosis
        C. fetus or C. jejuni
        ovine abortion
        Random hepatic necrosis - "Target" lesions
        Hepatosis Dietetica
        Pigs
        Vit. E./Se deficiency
        Young, rapid growers
        Acute submassive to massive necrosis
        Responses to Injury
        Regeneration
        ECM intact
        Repetetive affects structure and function
        Severe: Fibrosis
        Chronic injury
        Affects function
        "Cirrhosis"
        Bands of fibrosis: regenerative nodules and vascular abnormalities
        Intrahepatic portal hypertension -> acquired portosystemic shunts
        End stage disease
        Severe: Biliary Hyperplasia
        Non-specific response to many insults
        usually with biliary obstruction
        Liver Failure
        Acute
        Varied Clinical Signs
        Late stage
        Icterus
        Hepatic Encephalopathy
        CNS/Neuro abnormalities
        Behavioral changes
        Causes
        K9/F9: Congenital PS Shunt
        Ruminants/Horses: Hepatic Failure
        All species: Acquired PS Shunt, secondary to portal hypertension
        Incompletely understood metabolic encephalopathy
        Chronic
        Hypoalbuminemia
        Portal hypertension = ascites
        Acquired portosystemic shunts
        Impaired immune function
      - Chronic Hepatitis
        Granulomatous/Mycobacteria
        Progresses to Cirrhosis
        Usually toxins and Cu storage
        Neutrophils/Lymphocytes
      - Toxic Liver DIsease
        Acute
        Regeneration w/ ECM
        Chronic
        Fibrosis +/- Cirrhosis
        Most are predictable
        Some are just weird
        Pyrrolizidine alkaloids
        Plant Species
        Metabolised to active form in liver
        Binds to lipids, cross links DNA
        prevents cell division, but DNA synthesises
        Megalocytic hepatocytes
        Acute is rare
        Chronic most common
        Small amounts over long period
        Clinical Signs
        Megalocytosis
        Fibrosis
        Liver atrophy
        Phomopsin/lupinosis
        Fungus Diaporthe toxica
        Affects sheep most
        Binds to tubulin
        Inhibits microtubule assembly
        interfere with intracellular transport + mitosis
        Chronic most common
        Clinical Signs
        Small, hard, fibrotic liver
        Scattered necrosis
        Photosensitisation +/- HE
        NOT skeletal lupinosis
        Others
        Aflatoxins
        Amanita deathcap (fatal)
        Zamia palm
        Cu and Fe
        White phosphorus, rodenticide
      - Vascular Disturbances
        Anemia
        Atrophy/degeneration/necrosis
        Centrilobular
        Telangiectasis
        Incidental
        infarction
        Rare, usually lobar torsion
        Passive hyperemia (congestion)
        Disturbance of blood outflow
        RCHF
        Acute
        Chronic
        Also Ascites
        Congenital PSS
        Abnormal connection b/w portal and systemic
        blood bypasses liver to systemic
        intrahepatic (failed ductus venosus closure)
        large breed dogs
        Extrahepatic (vena cava)
        More common
        cats, small dogs
        single large calibre vessel
        NO PORTAL HYPERTENSION/ASCITES
        common in young dogs
        Microhepatica
        Portal hypertension
        Acquired PSS
        Increased portal pressure
        Prehepatic
        Uncommon
        Obstructed portal vein
        neoplasm/mass
        Intrahepatic
        Common
        Increased resistance to portal blood flow
        Liver disease
        portal vein hypoplasia
        Posthepatic
        Uncommon
        Increased resistance to hepatic outflow
        thrombosis/RCHF
        increased pressure = ascites
      - Hepatic Accumulations
        Fat
        Hepatic lipidosis
        Rounded lobes, greasy, friable
        Non-specific, many causes
        Excess TAG mobilisation
        Starvation
        Endocrinopathies
        Excess dietary intake
        Decreased energy for oxidation of fats
        Liver damage
        Decreased hepatic apoprotein synthesis
        decreased export/production of lipoprotein
        Liver damage
        Impaired secretion of lipoproteins
        Liver damage
        Examples
        Ketosis
        ruminants with high energy demands
        FFA from adipose oxidised to ketones in liver
        Bovine fatty liver syndrome
        Pregnancy toxemia
        Similar to ketosis
        Equine Hyperlipidemia
        Due to anorexia and stress
        Feline idiopathic hepatic lipidosis
        Leads to liver failure
        Endocrine disorders
        Diabetes mellitus
        Hypothyroidism
        Glycogen
        Diabetes Mellitus
        Glucocorticoid induced in dogs
        Hyperadrenocorticism
        Glycogen storage disease
        Pompes in Brahman cattle
        Copper
        3 stages
        Slow hepatic copper accumulation in lysosomes
        Hepatocellular Damage
        Hemolytic Crisis
        Stressful event
        Cu released to blood
        severe hemolytic anemia
        Death
        Icterus, dyspnea, haemoglobinuria/emia, renal failure, shock, death
        Progressive organelle damage
        Elevated liver enzymes
        excess diet intake
        Cholestasis prevents excretion
        Increasing clinical signs and severity
        Chronic
        hereditary in dogs
        Bedlington terriers
        Cu accumulates, causes necrosis and cirrhosis
        Amyloidosis
        Insoluble protein (B pleats)
        in space of Disse
        Affects most species
        Primary = inherited (RARE)
        Secondary = reactive to chronic inflammation (common)
        Enlarged, friable, firm waxy livers
      - Diseases of Proliferation
        HC benign nodular hyperplasia
        Common in Dogs >6y/o
        Idiopathic
        multiple lesions
        NOT clinically significant
        HC Neoplasia
        Adenoma
        Carcinoma
        Biliary Neoplasia
        Adenoma
        Carcinoma
        Other neoplasms
        Primary
        Fibrosarcoma/Haemangiosarcoma etc.
        Metastatic
        Liver common site
        Lymphoma/Haemangiosarcoma
  - Post hepatic: Cholestasis
    - Conjugated
    - Obstruction: pancreatitis/choleliths
    - Cholestatic Liver Disease
      - Jaundice
      - Photosensitisation
        Secondary (Type III), hepatogenous
        Hepatic dysfunction/biliary obstruction
        Impairs phylloerythrin excretion
      - Intrahepatic
        Most Common
        Decreased hepatocyte function
        hepatocytes swell, block canaliculi
        Inflammation +/- necrosis of ductules
      - Extrahepatic
        Block extrahepatic ducts
        Intraluminal: Choleliths/Parasites
        Extraluminal pressure: Neoplasia etc.
      - Lantana Toxicosis
        Liver Failure, Death
      - Sporodesmin Toxicosis
        Mycotoxin from fungus
        Perennial Rye Grass
        Facial eczema in ruminants
        Toxic to bile ducts, necrotic cholangitis
        Necrosis of biliary epithelium
        Ruminants: Left lobe boxing glove
- Use as indicative Tool
  - Mainly Cholestasis
    - Very specific in non-anemic patient
  - Very long half life/Persistent
- Horses
  - Mild to Moderate is a non-specific finding
  - Inappetence, decreased feed = increased unconjugated bilirubin
  - Increased plasma bilirubin w/ anorexia = decreased hepatic up-take
  - Resolves rapidly after resolution of anorexia
- Bilirubinuria
  - Dogs: LOW renal threshold
  - Cats: Higher renal threshold
Ammonia
- Produced in GIT by breakdown of AA + Urea
  - Transported to Liver via portal
    - Converted to Urea via urea cycle
- Volatile
- Collection and Handling
  - Immediately separate plasma
  - Chill/measure immediately
  - Limited diagnostic usefulness: Lability of specimen
- Ammonium Bi-urate crystals in urine
  - Normal in Dalmatians, CAN be in other breeds
  - Seen with increased blood ammonium levels
Cytology: FNA
- Ultra-sound guided
- Tells us:
  - Inflamm or Neoplasia
  - Nodular hyperplasia
  - Cholestasis
  - Lipid or Glycogen without hepatocytes
  - Interpretation is limited
Normal Anatomy
- Many lobes
- Cell Types
  - Hepatocytes
  - Endothelial
  - Kupffer
  - Biliary epithelial
  - Hepatic stellate cells
- Structure
  - Lobule
    - Hexagonal unit
    - Dual blood supply: From Portal Triad (periphery) towards Central vein (centre)
  - Acinus
    - Diamond shaped structure
    - Bile drains from hepatocytes to Portal Triad (centre)
  - Sinusoids
    - Low pressure
    - Extensive fenestration
    - Fibrosis changes anatomy = loss of function
Normal Function
- Bilirubin/Bile Acid metabolism > BILE
  - Emulsification of Fat
  - Eliminate waste: Bilirubin
  - Canaliculi -> intralobular bile ducts -> interlobular bile ducts -> hepatic duct -> gallbladder -> cystic duct -> Common bile duct -> Duodenum
- Carbohydrate and Lipid metabolism
- Xenobiotic metabolism
- Protein synthesis: albumin/clotting factors
- Immune function
Liver Dysfunction
- Bilirubin Secretion disturbance
  - Cholestasis -> Hyperbilirubinemia (Jaundice)
- Inadequate NH3 converted to Urea
  - Hepatic Encephalopathy
- Protein synthesis defect
  - Hypoalbuminemia
  - Low clotting factors
- Abnormal Carb/Fat metabolis
  - Hypoglycemia
  - Decreased cholesterol/hepatic lipidosis
- Acquired portosystemic shunting
- Consequences
  - Portal Hypertension
    - Ascites
  - Abnormal metabolism of chlorophyll
    - Secondary photosensitisation
  - Failure of Kupffer cell activity
    - Increased bacteria in circulation
  - Altered drug/chemical metabolism
  - Clinical Expression
    - Large functional reserve, 70-75% loss required. Acute or Chronic damage +/- failure Very variable Clinical signs
    - Lethargy/ill thrift
    - Abdominal distension/Ascites/hepatomegaly
    - CNS Signs (hepatic encephalopathy)
    - Inappetance/anorexia
    - V+/D+
    - Jaundice/Dark Urine
    - Abdominal Pain
    - Weight Loss
    - Secondary hemostatic disorder
    - Photosensitisation
    - Drug intolerance
Cholangitis
- Inflamm of bile ducts
  - Acute
  - Chronic
- Cholangiohepatitis
  - Extends to hepatic parenchyma
- Examples
  - Toxin: e.g. Sporodesmin
  - Neutrophilic
    - Ascending bacterial infection
      - Common in cats
  - Lymphocytic
    - In cats
    - Slowly progressive, v. chronic
    - Immune mediated?
    - usually concurrent pancreatitis
  - Destructive
    - occurs ind ogs
    - idiopathic
  - Parasitic (trematode)
    - Liver Flukes = fascioliasis
      - Acute
        Extensive necrosis/hemorrhage/inflammation
        Infectious necrotic hepatitis
        Bacillary haemoglobinuria
      - Chronic
        Chronic cholangiohepatitis
        peribiliary fibrosis
        fibrotic liver and loss of function

Informações

Descrição: VET377 Pathology Mapa Mental sobre Liver, criado por Bertrand Ng em 09-10-2017.
Criado por: Bertrand Ng
Visualizações: 6
Avaliação

Liver

Conteúdo do mapa

Informações

Fale Conosco

O que você acha do novo visual?